1. Field of the Invention
The present invention relates to an improved process for inactivating a virus which may be present in blood or blood products by treating the blood or blood product with a phthalocyanine dye under the influence of red light.
2. Description of the Related Art
Despite impressive reduction during the last decade in the risk of human pathogenic viruses as a result of blood transfusion, complete viral safety has not been achieved (R. Y. Dodd, "The risk of transfusion-transmitted infection", N. Eng. J. Med., 327, 419-421, 1992). Most of these viruses are lipid enveloped and their inactivation in cellular components of blood is the subject of intensive research.
Photochemical methods are the most promising for virus sterilization of platelets and red blood cells (RBC). For decontamination of platelet concentrates, UVA light and psoralens (PUVA) has been shown to be highly effective (L. Lin et al., "Use of 8-methoxypsoralen and long wavelength ultraviolet radiation for decontamination of platelet concentrates", Blood, 74, 517-525, 1989; R. Y. Dodd et al., "Inactivation of viruses in platelet suspensions that retain their in vitro characteristics: comparison of psoralen-ultraviolet A and merocyanine 540-visible light methods", Transfusion, 31, 483-490, 1991; and H. Margolis-Nunno et al., "Virus sterilization in platelet concentrates with psoralen and ultraviolet A light in the presence of quenchers", Transfusion, 32, 541-547, 1992).
For viral inactivation in RBC suspensions, red light (.lambda.&gt;600 nm) has to be used to avoid light absorption by hemoglobin. Following the pioneering work by Matthews et al. ("Photodynamic therapy of viral contaminants with the potential for blood banking applications", Transfusion, 28, 81-83, 1988) using HPD, other sensitizers with strong absorption in the far red have been employed (H. C. Neyndorff et al., "Development of a model to demonstrate photosensitizer mediated viral inactivation in blood", Transfusion, 30, 485-490, 1990; and M. M. Judy et al., "In vitro photodynamic inactivation of herpes simplex virus with sapphryins: 22.pi.-electron porphyrin-like macrocycles", Photochem. Photobiol., 53, 101-107, 1991).
Our laboratory has focused on the phthalocyanines as sensitizers for inactivation of lipid enveloped viruses (B. Horowitz et al., "Inactivation of viruses in blood with aluminum phthalocyanine derivatives", Transfusion, 31, 102-108, 1991; and E. Ben-Hur et al., "Photodynamic inactivation of retroviruses by phthalocyanines: the effect of sulfonation, metal ligand and fluoride", J. Photochem. Photobiol. B. Biol., 13, 145-152, 1992). To obtain maximum virucidal action while minimizing damage to RBC we have used two approaches. One was to screen for structural features of phthalocyanines that enhance viral inactivation and reduce RBC damage (E. Ben-Hur et al., "Phthalocyanine-induced photohemolysis: structure activity relationship and the effect of fluoride", Photochem. Photobiol., 58, 351-355, 1993; Z. Smetana et al., "Photodynamic inactivation of herpes viruses with phthalocyanine derivatives" J. Photochem. Photobiol. B. Biol., 22, 37-43, 1994; and S. Rywkin et al., "New phthalocyanines for photodynamic virus inactivation in red blood cell concentrates", Photochem. Photobiol., 60, 165-170, 1994). The second approach was to use scavengers of reactive oxygen species. It appears that quenchers of type I photodynamic reactions can reduce RBC damage without reducing virus inactivation (S. Rywkin et al., "Importance of type I and type II mechanisms in the photodynamic inactivation in blood with aluminum phthalocyanine derivatives", Photochem. Photobiol., 56, 463-469, 1992). This is presumably due to singlet oxygen being the primary mediator of virus killing while both types I and II reactions contribute to RBC damage. See also our earlier U.S. Pat. Nos. 5,120,649 and 5,232,844 and copending application Ser. Nos. 08/031,787, 08/344,919 and 08/364,031, the entire disclosures of which patents and applications are hereby incorporated by reference.
In spite of these advances, there remains a definite need in the art for new methods or improvements in existing methods which cause less RBC damage without also reducing virus kill.